Multi-well rotary synthesizer

ABSTRACT

An apparatus for synthesizing polymer chains includes a controller, a plurality of precision fit vials circularly arranged in multiple banks on a cartridge, a drain corresponding to each bank of vials, a chamber bowl, a plurality of valves for delivering reagents to selective vials, and a waste tube system for purging material from the vials. A purging operation can be selectively performed on one or more of the banks of vials. The multiple banks of valves provide an additional number of reagent choices while operating in a serial mode and faster reagent distribution while operating in a parallel mode. The plurality of vials are stored in the cartridge and are divided among individual banks wherein each bank of vials has a corresponding drain. There is at least one waste tube system for expelling the reagent solution from vials within a particular bank of vials when the waste tube system is coupled to the corresponding drain. The cartridge holding the plurality of vials rotates relative to the stationary banks of valves and the waste tube system. The controller rotates the cartridge and operates the banks of valves and the waste tube system in response to the required sequence of dispensing various reagent solutions and flushing appropriate vials in order to form the desired polymer chain within each vial.

FIELD OF THE INVENTION

[0001] The present invention relates to the field of synthesizers. Moreparticularly, this invention relates to synthesizers that utilizemultiple banks of vials to synthesize custom sequence definedoligonucleotides, polymers, and other organic compounds.

BACKGROUND OF THE INVENTION

[0002] Oligonucleotides are playing an increasingly important role indiagnostic medicine, forensic medicine, and molecular biology research.In addition to oligonucleotides, polymers such as peptides,polynucleotides, and other organic chains are also very important inscientific research.

[0003] Accordingly, the use of and demand for syntheticoligonucleotides, polymers, and organic chains has increased. In turn,this has spawned development of new synthesis systems and methods forbasic procedures for custom sequence defined oligonucleotides, polymers,and other organic chains.

[0004] Typically, the present automated systems and methods place asolid support such as controlled pore glass beads (CPG) into a pluralityof individual vials which provide a stable anchor to initiate thesynthesis process. Using a series of valves, the selected reagents aresequentially placed into the appropriate vial in a predeterminedsequence. Contact of the reagent with the CPG inside each of the vialscauses a reaction that results in sequenced growth thereon. Sequentialdeposits of the selected reagents within the vials build thepredetermined sequence.

[0005] A flushing procedure is typically utilized after a particularreagent is placed into one of the vials for a predetermined amount oftime. While the particular reagent contacts the CPG a reaction producesa sequenced growth on the CPG. In conventional synthesis machines theflushing procedure is performed on all the vials simultaneously. Duringa flushing operation within conventional synthesis machines, all thereagents within the plurality of individual vials are flushed andexpelled through a shared central orifice within the synthesis machine.After completion of a flushing operation, the plurality of vials arethen capable of receiving another reagent.

[0006] In High Throughput DNA Synthesis in a MultiChannel Format, L. E.Sindelar and J. M. Jaklevic teach an approach to high throughputparallel DNA synthesis in which a multi-vial format is utilized. Thereactions are carried out in open vials. Each vial contains CPG to formthe substrate for the synthesis and a high density filter bottom toretain the CPG within each vial. There is a common vacuum line that iscoupled to all the vials. This common vacuum line simultaneously flushesthe material contained within all the vials. The synthesis of a DNAsequence is carried out by directly dispensing reagents into individualreaction vials. A computer controls the sequence in which reagents aredispensed and timing periodic flushing operations to expel material fromthe reaction vials.

[0007] U.S. Pat. No. 5,529,756, by Brennan, teaches an apparatus andmethod for polymer synthesis utilizing arrays. This apparatus includesan array of nozzles with each nozzle coupled to a reservoir containing areagent and a base assembly having an array of reaction vials. Atransport mechanism aligns the reaction vials and selected nozzles todeposit an appropriate reagent to a selected vial. Each of the reactionvials has an inlet for receiving a reagent and an outlet for expelling amaterial. To perform a flushing operation, this apparatus creates apressure differential between the inlet and outlet of the array ofvials. During the flushing operation, material within each of the arrayof vials are simultaneously expelled.

[0008] A retaining device is customarily utilized to ensure that the CPGremains within the corresponding vial during the flushing procedure.This retaining device is located within each individual vial and ispositioned to prevent the CPG from exiting the orifice during theflushing procedure.

[0009] Conventional automated synthesis systems perform the flushingoperation simultaneously on all vials within the system. Conventionalautomated synthesis systems lack the ability to selectively perform theflushing operation on groups of vials within the system.

[0010] What is needed is a synthesizer that is configured to selectivelyperform depositing and flushing operations on groups of vials within thesystem.

SUMMARY OF THE INVENTION

[0011] A multi-well rotary synthesizer includes a controller, aplurality of precision fit vials circularly arranged in multiple bankson a cartridge, a drain corresponding to each bank of vials, a chamberbowl, a plurality of valves for delivering reagents to selective vials,and a waste tube system for purging material from the vials. The banksof vials can be selectively purged, allowing the banks of vials to beused to synthesize different polymer chains. Further, the multiple banksof valves provide an additional number of reagent choices whileoperating in a serial mode and faster reagent distribution whileoperating in a parallel mode.

[0012] The plurality of vials are held within the cartridge and aredivided among individual banks. Preferably, each individual bank ofvials has a corresponding drain. There is at least one waste tube systemfor expelling the reagent solution from vials within a particular bankof vials when the waste tube system is coupled to the correspondingdrain. The cartridge holding the plurality of vials rotates relative tothe stationary banks of valves and the waste tube system. The controllercontrols a motor to rotate the cartridge. The controller also operatesthe banks of valves and the waste tube system in response to therequired sequence of dispensing various reagent solutions and flushingappropriate vials in order to create the desired polymer chain.

[0013] A frit is inserted into each vial and serves as a filter and tohold the CPG within the vial. The interior of each vial is precisionbored to ensure a tight consistent seal with the corresponding frit.This consistent seal with the frit for every vial also results in aconsistent reagent solution flow through every vial. The exterior ofeach vial also has a precise dimension to consistently fit within thecartridge and provide a pressure tight seal around each vial within thecartridge.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014]FIG. 1 illustrates a perspective view of the synthesizer of thepresent invention.

[0015]FIG. 2 illustrates the preferred cartridge of the presentinvention.

[0016]FIG. 3 illustrates a perspective view of an alternate cartridge.

[0017]FIG. 4 illustrates a cross-sectional view of the synthesizer ofthe present invention.

[0018]FIG. 5 illustrates a top view of the drain plate.

[0019]FIG. 6 illustrates a cross-sectional view of the vial.

[0020]FIG. 7 illustrates a cross-sectional view of the waste tubesystem.

[0021]FIG. 8 illustrates the controlling computer coupled to thesynthesizer of the preferred embodiment of the present invention.

[0022]FIG. 9 illustrates a cross-sectional view of an alternate wastetube system.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

[0023] While the present invention will be described with reference toseveral specific embodiments, the description is illustrative of thepresent invention and is not to be construed as limiting the invention.Various modifications to the present invention can be made withoutdeparting from the scope and spirit of the present invention. For thesake of clarity and a better understanding of the present invention,common components share common reference numerals throughout variousfigures.

[0024]FIG. 1 illustrates a synthesizer 100. The synthesizer 100 isdesigned for building a polymer chain by sequentially adding polymerunits to a solid support in a reagent solution. The solid supportgenerally resides within a vial and various reagent solutions aresequentially added to the vial. Before an additional reagent solution isadded to the vial, the previous reagent solution is preferably purgedfrom the vial. Although, the synthesizer 100 is particularly suited forbuilding sequence defined oligonucleotides, the synthesizer 100 is alsoconfigured to build any other desired polymer chain or organic compound.The term “polymer chain” is defined as a unit that is bound to otherunits of the same or different kind to form a polymer chain, such asoligonucleotides and peptide chains. It is important to note thatalthough the present invention is described in context of specificapplications, the present invention should not be limited to thesespecific examples disclosed herein.

[0025] The synthesizer 100 preferably comprises at least a bank ofvalves and at least one bank of vials. Within each bank of vials, thereis at least one vial for holding the solid support and for containing areagent solution such that a polymer chain can be synthesized. Withinthe bank of valves, there are preferably a plurality of valvesconfigured for selectively dispensing a reagent solution into one of thevials. The synthesizer 100 is preferably configured to allow each bankof vials to be selectively purged of the presently held reagentsolution. Additional banks of valves provide the synthesizer 100 withgreater flexibility. For example, each bank of valves can be configuredto distribute reagent solutions to a particular bank of vials in aparallel fashion to minimize the processing time. Alternatively,multiple banks of valves can be configured to distribute reagentsolutions to a particular bank of vials in series thus allowing thesynthesizer 100 to hold a larger number of different reagent solutions,thus being able to create complex polymer chains.

[0026]FIG. 1 illustrates an exterior perspective view of a rotarysynthesizer 100. As illustrated in FIG. 1, the synthesizer 100 includesa base 105, a cartridge 170, a first bank of vials 115, a second bank ofvials 125, a plurality of dispense lines 140, a plurality of fittings150, a first bank of valves 110 and a second bank of valves 120. Withineach of the banks of valves 110 and 120, there is preferably at leastone valve. Within each of the banks of vials 115 and 125, there ispreferably at least one vial. Each of the valves is capable ofselectively dispensing a reagent solution into one of the vials. Asstated before, each of the vials is preferably configured for retaininga solid support such as CPG and holding a reagent solution. Further, aseach reagent solution is sequentially deposited within the vial andsequentially purged therefrom, a polymer chain is generated.

[0027] Preferably, there is a plurality of reservoirs (not shown) eachcontaining a specific reagent solution to be dispensed to one of theplurality of valves 130. Each of the valves within the first bank andsecond bank of valves 110 and 120, is coupled to a correspondingreservoir. Each of the plurality of reservoirs is pressurized. As aresult, as each valve is opened, a particular reagent solution from thecorresponding reservoir is dispensed to a corresponding vial.

[0028] Each of the plurality of dispense lines 140 is coupled to acorresponding one of the valves within the first and second banks ofvalves 110 and 120. Each of the plurality of dispense lines 140 providesa conduit for transferring a reagent solution from the valve to acorresponding vial. Each one of the plurality of dispense lines 140 ispreferably configured to be flexible and semi-resilient in nature.Preferably, the plurality of dispense lines 140 are each coated withTeflon® which is more resistant to deterioration upon contact withreagent solutions and provides an adequate seal between the plurality ofvalves 130 and the plurality of fittings 150. Further, each of theplurality of fittings 150 is preferably coupled to one of the pluralityof dispense lines 140. The plurality of fittings 150 are preferablyconfigured to prevent the reagent solution from splashing outside thevial as the reagent solution is dispensed from a cap to a particularvial positioned below the cap.

[0029] As shown in FIG. 1, the first and second banks of valves 110 and120 each have thirteen valves. In FIG. 1, the number of valves in eachbank is merely for exemplary purposes. It is preferable to have fifteenvalves for each bank even though the illustrated cartridge 170 only hastwelve vials per bank. The present invention provides greaterflexibility in creating complex polymer chains by including a greaternumber of valves than vials per bank. It should be apparent to thoseskilled in the art that any appropriate number of valves can be includedwithin each bank of valves.

[0030] Each of the vials within the first bank of vials 115 and thesecond bank of vials 125 is presently shown resting in one of aplurality of receiving holes 185 within the cartridge 170. Preferably,each of the vials within the corresponding plurality of receiving holes185 is positioned in a substantially vertical orientation. Each of thevials is configured to retain a solid support such as CPG and hold areagent solution. Preferably CPG is utilized as this solid support.Alternatively, any other appropriate solid support can be used tosupport the polymer chain being synthesized.

[0031] In use, each of the valves selectively dispenses a reagentsolution through one of the plurality of dispense lines 140 and fittings150. The first and second banks of valves 110 and 120 are preferablycoupled to the base 105 of the synthesizer 100. The cartridge 170 whichcontains the plurality of vials 181 rotates relative to the synthesizer100 and relative to the first and second banks of valves 110 and 120. Byrotating the cartridge 170, a particular vial 181 can be positionedunder a specific valve such that the corresponding reagent solution fromthis specific valve is dispensed into this vial. Further, the first andsecond banks of valves 110 and 120 are capable of simultaneously andindependently dispensing reagent solutions into corresponding vials.

[0032]FIG. 2 illustrates a detailed view of the cartridge 170.Preferably, the cartridge 170 is circular in shape such that thecartridge 170 is capable of rotating in a circular path relative to thebase 105 and the first and second banks of valves 110 and 120. Thecartridge 170 has a plurality of receiving holes 185 on its uppersurface around the peripheral edge of the cartridge 170. Each of theplurality of receiving holes 185 is configured to hold one of the vials181 within the first bank of vials 115 and the second bank of vials 125.The plurality of receiving holes 185 as shown on the cartridge 170 aredivided up among four banks. A bank 180 illustrates one of the fourbanks on the cartridge 170 and contains twelve receiving holes whereineach receiving hole is configured to hold a vial. An exemplary vial 181is shown being inserted into one of the plurality of receiving holes185. The total number of receiving holes shown on the cartridge 170includes forty-eight (48) receiving holes divided into four banks oftwelve receiving holes each. The number of receiving holes and theconfiguration of the banks of receiving holes is shown on the cartridge170 for exemplary purposes only. It should be apparent to those skilledin the art that any appropriate number of receiving holes and banks ofreceiving holes can be included in the cartridge 170. Preferably, thereceiving holes 185 within the cartridge each have a precise diameterfor accepting the vials 181, which also each have a correspondingprecise exterior dimension to provide a pressure-tight seal when thevials 181 are inserted into the receiving holes 185.

[0033]FIG. 3 illustrates an alternative cartridge 300. The cartridge 300is similar to the cartridge 170 shown in FIGS. 1 and 2. Each of thereceiving holes 320 is configured to hold a vial 181. A plurality ofreceiving holes are grouped together to form a bank of receiving holes310. The cartridge 300 contains a total of ninety-six (96) receivingholes grouped into twelve banks, each bank including eight receivingholes. The number of receiving holes and the configuration of the banksof receiving holes included on the cartridge 300 is exemplary only.

[0034]FIG. 4 illustrates a cross sectional view of the synthesizer 100.As illustrated in FIG. 4, the synthesizer 100 includes the base 105, aset of valves 470, a motor 445, a gear box 440, a chamber bowl 400, adrain plate 410, a drain 740, the cartridge 170, a chamber seal 450, amotor connector 465, a waste tube system 430, a controller 480, and aclear window 460. The valves 470 are coupled to the base 105 of thesynthesizer 100 and are preferably positioned above the cartridge 170around the outside edge of the base 105. This set of valves 470preferably contains fifteen individual valves which each deliver acorresponding reagent solution in a specified quantity to a vial held inthe cartridge 170 positioned below the valve. Each of the valves maydispense the same or different reagent solutions depending on theuser-selected configuration. When more than one valve dispenses the samereagent solution, the set of valves 470 is capable of simultaneouslydispensing a reagent solution to multiple vials within the cartridge170. When the valves 470 each contain different reagent solutions, eachone of the valves 470 is capable of dispensing a corresponding reagentsolution to any one of the vials within the cartridge 170.

[0035] Although not specifically shown in FIG. 4, the synthesizer 100may have multiple sets of valves. The plurality of valves within themultiple sets of valves may be configured in a variety of ways todispense the reagent solutions to a select one or more of the vials. Forexample, in one configuration, where each set of valves is identicallyconfigured, the synthesizer 100 is capable of simultaneously dispensingthe same reagent solution in parallel from multiple sets of valves tocorresponding banks of vials. In this configuration, the multiple banksof vials may be processed in parallel. In the alternative, eachindividual valve within multiple sets of valves may contain entirelydifferent reagent solutions such that there is no duplication of reagentsolutions among any individual valves in the multiple sets of valves.This configuration allows the synthesizer 100 to build polymer chainsrequiring a large variety of reagent solutions without changing thereagent solutions associated with each valve.

[0036] The motor 445 is preferably mounted to the base 105 through thegear box 440 and the motor connector 465. The chamber bowl 400preferably surrounds the motor connector 465 and remains stationaryrelative to the base 105. The chamber bowl 400 is designed to hold anyreagent solution spilled from the plurality of vials 160 during thepurging process. Further, the chamber bowl 400 is configured with a tallshoulder to insure that spills are contained within the bowl 400. Thechamber lip seal 450 preferably provides a seal around the motorconnector 465 in order to prevent the contents of the chamber bowl 400from flowing into the gear box 440. The chamber seal 450 is preferablycomposed of a flexible and resilient material such as Teflon® orelastomer which conforms to any irregularities of the motor connector465. Alternatively, the chamber seal can be composed of any otherappropriate material. Additionally, the chamber seal 450 hasfrictionless properties which allow the motor connector 465 to rotatefreely within the seal. For example, coating this flexible material withTeflon® helps to achieve a low coefficient of friction.

[0037] The drain plate 410 is coupled to the motor connector 465. Thecartridge 170 is coupled to the drain plate 410. More specifically, thedrain plate 410 is attached to the motor connector 465 which rotates thedrain plate 410 while the motor 445 is operating and the gear box 440 isturning. The cartridge 170 and the drain plate 410 are preferablyconfigured to rotate as a single unit. The drain plate 410 is configuredto catch and direct the reagent solutions as the reagent solutions areexpelled from the plurality of vials. While operating, the motor 445 isconfigured to rotate both the cartridge 170 and the drain plate 410through the gear box 440 and the motor connector 465. The chamber seal450 allows the motor connector 465 to rotate the cartridge 170 and thedrain plate 410 through a portion of the chamber bowl 400 while stillcontaining any reagent solutions in the chamber bowl 400.

[0038] The controller 480 is coupled to the motor 445 to activate anddeactivate the motor 445 in order to rotate the cartridge 170 and thedrain plate 410. The controller 480 provides embedded control to thesynthesizer and controls not only the operation of the motor 445, butalso the operation of the valves 470 and the waste tube system 430.

[0039]FIG. 5 illustrates a detailed top view of the drain plate 410. Thedrain plate 410 has a plurality of securing holes 780 for attaching tothe motor connector 465. The drain plate 410 also has a top surface 715which attaches to the underside of the cartridge 170. As statedpreviously, the cartridge 170 holds the plurality of vials grouped intothe plurality of banks.

[0040] The drain plate 410 preferably has four collection areas 705,710, 720 and 730, to correspond to the four banks within the cartridge170. Each of these four collection areas 705, 710, 720 and 730 forms arecessed area below the top surface 715 and is designed to contain anddirect material flushed from the vials within the bank above thecollection area. Each of the four collection areas 705, 710, 720 and 730is positioned below a corresponding one of the banks of vials on thecartridge 170. The drain plate 410 is rotated with the cartridge 170 tokeep the corresponding collection area below the corresponding bank.

[0041] There are four drains 740, 750, 760 and 770, each of which islocated within one of the four collection areas 705, 710, 720 and 730,respectively. In use, the collection areas 705, 710, 720 and 730 areconfigured to contain material flushed from corresponding vials and passthat material through the drains 740, 750, 760 and 770, respectively.Preferably, there is a collection area and a drain corresponding to eachbank of vials within the cartridge 170. Alternatively, any appropriatenumber of collection areas and drains can be included within a drainplate.

[0042] The clear window 460 (FIG. 4) is attached to a top plate of thebase 105 and covers the area above the cartridge 170. The top plate ofthe base 105 opens up allowing an operator or maintenance person accessto the interior of the synthesizer 100. The clear window 460 allows theoperator to observe the synthesizer 100 in operation while providing apressure sealed environment within the interior of the synthesizer 100.As shown in FIG. 4, there are a plurality of through holes 520 in theclear window 460 to allow the plurality of dispense lines 140 to extendthrough the clear plate 460 to dispense material into the vials.

[0043] The clear window 460 also includes a gas fitting 530 attachedtherethrough. The gas fitting 530 is coupled to a gas line 540. The gasline 540 preferably continuously emits a stream of inert gas which flowsinto the synthesizer 100 through the gas fitting 530 and flushes outtraces of air and water from the plurality of vials 160 within thesynthesizer 100. Providing the inert gas flow through the gas fitting530 into the synthesizer 100 prevents the polymer chains being formedwithin the vials from being contaminated without requiring the pluralityof vials 160 to be hermetically sealed and isolated from the outsideenvironment.

[0044] The drain 740 is attached to the drain plate 410 and ispositioned to correspond with a bank of vials held within the cartridge170. The drain 740 corresponds to a single bank of vials and isprimarily utilized for flushing material from this single bank of vials.As described above, preferably, each bank of vials has a correspondingdrain.

[0045] The waste tube system 430 is preferably utilized to provide apressurized environment for flushing material including reagentsolutions from the plurality of vials located within a correspondingbank of vials and expelling this material from the synthesizer 100.Alternatively, the waste tube system 430 can be used to provide a vacuumfor drawing material from the plurality of vials located within acorresponding bank of vials.

[0046] An isolated cross-sectional view of the waste tube system 430 isillustrated in FIG. 7. The waste tube system 430 comprises a stationarytube 490 and a mobile waste tube 500. The stationary tube 490 and themobile waste tube 500 are slidably coupled together. The stationary tube490 is attached to the chamber bowl 410 and does not move relative tothe chamber bowl 400. In contrast, the mobile tube 500 is capable ofsliding relative to the stationary tube 490 and the chamber bowl 400.When in an inactive state, the waste tube system 430 does not expel anyreagent solutions. During the inactive state, both the stationary tube490 and the mobile tube 500 are preferably mounted flush with the bottomportion of the chamber bowl 400.

[0047] When in an active state, the waste tube system 430 purges thematerial from the corresponding bank of vials. During the active state,the mobile tube 500 rises above the bottom portion of the chamber bowl400 towards the drain plate 410. The drain plate 410 is rotated over toposition a drain corresponding to the bank to be flushed, above thewaste tube system 430. The mobile tube 500 then couples to this drainand the material is flushed out of the corresponding bank of vials andinto the drain plate 420. The reagent solution is purged from thecorresponding bank of vials due to a sufficient pressure differentialbetween a top opening 610 (FIG. 6) and a bottom opening 640 (FIG. 6) ofeach vial. This sufficient pressure differential is preferably createdby coupling the mobile waste tube 500 to the corresponding drain.Alternatively, the waste tube system 430 may also include a vacuumdevice 510 coupled to the stationary tube 490 wherein the vacuum device510 is configured to provide this sufficient pressure differential toexpel material from the corresponding bank of vials. When thissufficient pressure differential is generated, the excess materialwithin the vials being flushed, then flows through the correspondingdrain and is carried away via the waste tube system 430.

[0048] When engaging the corresponding drain to flush a bank of vials,preferably the mobile tube 500 slides over the corresponding drain suchthat the mobile tube 500 and the drain act as a single unit.Alternatively, as illustrated in FIG. 9 the waste tube system 530includes a mobile tube 520 which engages the corresponding drain bypositioning itself directly below the drain and then sealing against thedrain without sliding over the drain. The mobile tube 520 includes adrain seal 540 positioned on top of the mobile tube 520. In thisembodiment, during a flushing operation, the mobile tube 520 is notlocked to the corresponding drain. In the event that this drain isaccidentally rotated while the mobile waste tube 520 is engaged with thedrain, the drain and mobile tube 500 of the synthesizer 100 will simplydisengage and will not be damaged. If this occurs while material isbeing flushed from a bank of vials, any spillage from the drain iscontained within the chamber bowl 400.

[0049] Configuring the waste tube system 430 to expel the reagentsolution while the mobile waste tube 500 is coupled to the drain allowsthe present invention to selectively purge individual banks of vials.Instead of simultaneously purging all the vials within the synthesizer100, the present invention selectively purges individual banks of vialssuch that only the vials within a selected bank or banks are purged.

[0050] Preferably, the synthesizer 100 includes two waste tube systems430 for flushing two banks of vials simultaneously. Alternatively, anyappropriate number of waste tube systems can be included within thesynthesizer 100 for selectively flushing- banks of vials.

[0051]FIG. 6 illustrates a cross sectional view of a vial 181. The vial181 is an integral portion of the synthesizer 100. Generally, thepolymer chain is formed within the vial 181. More specifically, the vial181 holds a CPG 650 on which the polymer chain is grown. As statedpreviously, to create the polymer chain, the CPG 650 is sequentiallysubmerged in various reagent solutions for a predetermined amount oftime. With each deposit of a reagent solution, an additional unit isadded to the resulting polymer chain. Preferably, the CPG 650 is heldwithin the vial 181 by a frit 620. The vial 181 includes a top opening610 and a bottom opening 640. During the dispensing process, the vial181 is filled with a reagent solution through the top opening 610. Then,during the purging process, the vial 181 is drained of the reagentsolution through the bottom opening 640. The frit 620 prevents the CPG650 or other support from being flushed away during the purging process.A precision bored interior 630 holds the frit 620 in place and providesa consistent compression and seal with the frit 620. As a result of theprecision bored interior 630, there is a consistent flow of the reagentsolution through each vial during both the dispensing and purgingprocesses.

[0052] The exterior of each vial 181 also has a precise dimension aroundthe support 660. This support 660 fits within the receiving hole 185within the cartridge 170 and provides a pressure tight seal around eachvial within the cartridge 170. Preferably, each vial 181 is formed ofpolyethylene by a molded process. Alternatively, the vials 181 can beformed using any appropriate process and any appropriate material.

[0053] In use, the controller 480 which is coupled to the motor 445, thevalves 470, and the waste tube system 430 coordinates the operation ofthe synthesizer 100. The controller 480 controls the motor 445 such thatthe cartridge is rotated to align the correct vials with the dispenselines 140 corresponding to the appropriate valves 470 during dispensingoperations and that the correct one of the drains 740, 750, 760 and 770,are aligned with an appropriate waste tube system 430 during a flushingoperation.

[0054]FIG. 8 illustrates a computer system 800 coupled to thesynthesizer 100. The computer system 800 preferably provides thesynthesizer 100 and specifically the controller 480 with operatinginstructions. These operating instructions include rotating thecartridge 170 to a predetermined position, dispensing one of a pluralityof reagent solutions into selected vials through the valves 470 anddispense lines 140, flushing the first bank of vials 115 and/or thesecond bank of vials 125, and coordinating a timing sequence of thesesynthesizer functions. Preferably, the computer system 800 allows theuser to input data representing reagent solution sequences to form apolymer chain, oligonucleotides, and other organic compounds via agraphical user interface. After the user inputs this data, the computersystem 800 instructs the synthesizer 100 to perform appropriatefunctions without any further input from the user. The computer system800 preferably includes a processor 810, an input device 820 and adisplay 830. The computer 800 can be configured as a laptop or adesktop.

[0055] The present invention forms custom defined sequences such asoligonucleotides, polymers and other organic compounds. The presentinvention has a plurality of vials divided among a plurality of bankswherein a custom sequence can be synthesized within each vial. Thepresent invention forms these custom sequences without constantsupervision by the user.

[0056] Each bank of vials has a drain and can be selectively purged. Toperform a purging operation, the drain of the corresponding bank ofvials is coupled to a mobile waste tube. After coupling the drain to themobile waste tube, a pressure differential is formed and the materialwithin each of the vials within the corresponding bank of vials isexpelled.

[0057] The present invention preferably utilizes a plurality of valvesdivided into a plurality of banks of valves to perform a fillingoperation to dispense reagent solutions to various vials during thefilling operation. Each of the plurality of valves can be configured todispense different reagent solutions to form complex custom sequences.In a parallel configuration, the plurality of valves can be configuredto dispense the same reagent solution simultaneously to more than onevial.

[0058] The present invention allows the user to enter the customsequence into a computer system. This computer system controls the filloperation and the purge operation such that appropriate vials are filledwith the correct reagent solutions and the appropriate banks of vialsare purged at the appropriate times within the sequence. Further, thecomputer system ensures that the correct quantity of reagent solution isdeposited and that the reagent solution remains in the appropriate vialfor the correct amount of time.

[0059] Each vial of the present invention has a precision bored interiorthat is configured to produce a consistent seal with a frit. By havingthe consistent seal with the frit, the reagent solutions flow evenly andpredictably through each vial of the present invention. Each vial alsoincludes a precise exterior dimension to consistently fit within thecartridge and provide a pressure tight seal around the vial within thecartridge.

[0060] In operation, when building sequence defined oligonucleotides,polymer chains or other organic compounds, the synthesizer 100 rotatesthe appropriate vials under the dispense tubes corresponding to theappropriate valves 470 at the appropriate times to build the desiredsequence or compound. The synthesizer also rotates the banks of vialsover a corresponding waste tube system 430 in order to flush materialfrom the vials, as appropriate. As discussed above, the banks of vialsheld within a cartridge can be selectively purged to allow a user topotentially build different sequences or compounds within each vial. Inthis manner, one bank of vials can be purged, while another bank ofvials is in a wait period. While purging one bank of vials, a dispenseoperation could also be performed on vials other than the bank or banksof vials being purged, if the position of the vials corresponds to theappropriate valves. However, during a purging operation, the cartridge170 cannot be rotated or the drain 740 will disengage from the mobilewaste tube 500.

[0061] To perform a dispense operation for a selected vial, the motor445 rotates the cartridge 170 in response to the computer system 800such that the vial 181 is positioned below the appropriate dispense line140 corresponding to the valve 470. Once the vial 181 is properlypositioned below this dispense line 140, the valve is opened by thecontroller 480 and the solution controlled by the valve 470 flowsthrough the dispense tube 140 into the vial 181. The valve 470 is thenclosed after a predetermined period of time corresponding to the preciseamount of solution to be dispensed into the vial 181.

[0062] To purge material from a bank of vials, the motor 445 rotates thecartridge 170 in response to the computer system 800 such that the draincorresponding to the bank of vials to be purged is positioned above thewaste tube system 430. The mobile waste tube 500 is then raised toengage the drain and the material within the bank of vials is expelledfrom the vials through the waste tube system 430.

[0063] The present invention has been described in terms of specificembodiments incorporating details to facilitate the understanding of theprinciples of construction and operation of the invention. Suchreference herein to specific embodiments and details thereof is notintended to limit the scope of the claims appended hereto.

[0064] It will be apparent to those skilled in the art thatmodifications may be made in the embodiment chosen for illustrationwithout departing from the spirit and scope of the invention.Specifically, it will be apparent to one of ordinary skill in the artthat the device of the present invention could be implemented in severaldifferent ways and the embodiments disclosed above are only exemplary ofthe preferred embodiment and the alternate embodiments of the inventionand is in no way a limitation.

We claim:
 1. A synthesizer for forming a polymer chain by sequentiallyadding monomer units found in one of a plurality of reagent solutions,the synthesizer comprising: a. a first vial and a second vial, whereinthe first vial and the second vial are configured for holding theplurality of reagent solutions; b. means for dispensing configured fordispensing the plurality of reagent solutions into the first and secondvials; and c. means for selectively expelling material from the firstand second vials, configured for coupling to the first and second vialsand purging material from a selective one of the first vial and thesecond vial.
 2. The synthesizer according to claim 1 further comprisinga cartridge configured for holding the first vial and the second vial.3. The synthesizer according to claim 2 wherein the cartridge holds thefirst vial and the second vial along a circular perimeter of thecartridge.
 4. The synthesizer according to claim 3 further comprising amotor coupled to the cartridge configured for selectively rotating thecartridge relative to the means for sequentially dispensing.
 5. Thesynthesizer according to claim 4 further comprising a drain platecoupled to the cartridge for separating the first vial into a first bankof vials and the second vial into a second bank of vials.
 6. Thesynthesizer according to claim 1 further comprising a chamber bowlcoupled to the means for selectively expelling wherein the chamber bowlcontains any spilled material.
 7. The synthesizer according to claim 6further comprising a seal coupled to the chamber bowl to prevent spilledmaterial from escaping outside the chamber bowl.
 8. The synthesizeraccording to claim 1 wherein the means for selectively expelling furthercomprises: a. means for forming a pressure differential between a firstopening and a second opening of the selective one of the first vial andthe second vial; and b. a waste tube to collect material expelled fromthe selective one of the first vial and the second vial.
 9. Thesynthesizer according to claim I wherein the means for dispensingfurther comprises: a. a plurality of valves for controlling dispensingof the plurality of reagent solutions; and b. a plurality of dispenselines wherein each of the plurality of the dispense lines is coupled toa corresponding one-of the plurality of valves for delivering one of theplurality of reagent solutions to a selected vial.
 10. The synthesizeraccording to claim 1 wherein each of the first vial and the second vialfurther comprise a precision bored interior configured to hold a fritfor retaining a solid material above the frit, and further wherein thefirst vial and the second vial are configured to maintain a consistentflow through the precision bored interior.
 11. A synthesizer for forminga polymer chain by sequentially adding monomer units found in aplurality of reagent solutions, the synthesizer comprising: a. a firstvial configured to hold the plurality of reagent solutions; b. a secondvial configured to hold the plurality of reagent solutions; c. acartridge to hold the first vial and the second vial; d. a dispensingsystem to dispense the plurality of reagent solutions into the first andsecond vials; and e. a purging system to remove material from aselective one of the first vial and the second vial.
 12. The synthesizeraccording to claim 11 wherein the cartridge holds the first vial and thesecond vial along a circular perimeter of the cartridge.
 13. Thesynthesizer according to claim 11 further comprising a chamber bowlcoupled to the purging system wherein the chamber bowl contains spilledmaterial.
 14. The synthesizer according to claim 13 further comprising aseal coupled to the chamber bowl to prevent spilled material fromescaping outside the chamber bowl.
 15. The synthesizer according toclaim 11 wherein the purging system further comprises: a. means forforming a pressure differential between a first opening and a secondopening of the selective one of the first vial and the second vial; andb. a waste tube to collect material expelled from the selective one ofthe first vial and the second vial.
 16. The synthesizer according toclaim 11 wherein the dispensing system further comprises: a. a pluralityof valves for controlling dispensing of the plurality of reagentsolutions; and b. a plurality of dispense lines each coupled to one ofthe plurality of valves for delivering a corresponding one of thereagent solutions to a selected vial.
 17. The synthesizer according toclaim 11 wherein each of the first vial and the second vial furthercomprise a precision bored interior configured to hold a frit forretaining a solid material above the frit, and further wherein the firstvial and the second vial are configured to maintain a consistent flowthrough the precision bored interior.
 18. The synthesizer according toclaim 11 further comprising a drain plate coupled to the cartridge forseparating the first vial into a first bank of vials and the second vialinto a second bank of vials.
 19. The synthesizer according to claim 11further comprising a motor coupled to the cartridge to selectivelyrotate the cartridge relative to the dispensing system.
 20. Asynthesizer for creating a polymer chain by sequentially adding monomerunits found in one of a plurality of reagent solutions, the synthesizercomprising: a. a plurality of vials wherein each of the plurality ofvials is configured to hold material including the plurality of reagentsolutions; b. a cartridge for holding the plurality of vials anddividing the plurality of vials into a first bank of vials including atleast one of the plurality of vials and a second bank of vials includingat least one of the plurality of vials; c. a dispensing systemconfigured to sequentially dispense selective ones of the plurality ofreagent solutions into the plurality of vials; and d. a purging systemconfigured to selectively purge material from the first bank of vialsand the second bank of vials.
 21. The synthesizer according to claim 20further comprising a first drain coupled to the first bank of vials anda second drain coupled to the second bank of vials, the first and seconddrains each configured for selectively coupling with the purging systemfor draining the first bank of vials and the second bank of vials. 22.The synthesizer according to claim 21 wherein the purging system furthercomprises a waste tube capable of selectively coupling with a selectiveone of the first drain and the second drain to purge material from thefirst bank of vials and the second bank of vials.
 23. The synthesizeraccording to claim 20 wherein the dispensing system further comprises:a. a plurality of valves for controlling the dispensing of the pluralityof reagent solutions; and b. a plurality of dispense lines each coupledto one of the plurality of valves for delivering a corresponding one ofthe plurality of reagent solutions to a selected vial.
 24. A purgingsystem configured for use with a synthesizer containing a first bank ofvials and a second bank of vials wherein the first bank of vials has afirst drain and the second bank of vials has a second drain, the purgingsystem comprising: a. a pressurizing system for creating a pressuredifferential within a selective one of the first bank of vials and thesecond bank of vials; and b. a first waste tube capable of coupling witha selective one of the first drain to purge material from the first bankof vials and the second drain to purge material from the second bank ofvials.
 25. The purging system according to claim 24 further comprising adrain seal coupled to the first waste tube for creating a flexible sealbetween the first waste tube and the selective one of the first drainand the second drain.
 26. The purging system according to claim 24further comprising a second waste tube capable of selectively couplingwith the first drain to purge the material from the first bank of vialsand the second drain to purge the material from the second bank of vialswherein the purging system is capable of selectively and simultaneouslypurging the first bank of vials and the second bank of vials.
 27. A vialcomprising a precision bored interior configured to hold a frit forretaining material within the vial above the frit and maintain aconsistent flow through the precision bored interior during a flushingprocedure.
 28. The vial according to claim 27 further comprising anexterior dimension configured to fit within a receiving hole of acartridge, thereby providing a pressure-tight seal between the vial andthe cartridge.
 29. A vial comprising an exterior dimension configured tofit within a receiving hole of a cartridge thereby providing apressure-tight seal between the vial and the cartridge and a precisionbored interior to maintain a consistent flow through the precision boredinterior during a flushing procedure.
 30. The vial according to claim 29further comprising a frit positioned within the precision bored interiorto retain material within the vial above the frit.
 31. A method ofselectively and sequentially dispensing a plurality of reagent solutionsto a plurality of vials divided into a first bank of vials and a secondbank of vials and selectively purging material from the first bank ofvials and the second bank of vials, comprising the steps of: a.dispensing one or more of the plurality of reagent solutions to aselective one or more of the plurality of vials; and b. purging materialfrom a selective one of the first bank of vials and the second bank ofvials.
 32. The method according to claim 31 wherein during the step ofdispensing one of the plurality of reagent solutions is dispensed intoone or more of the plurality of vials in a parallel fashion.
 33. Themethod according to claim 31 wherein during the step of dispensing oneor more of the plurality of reagent solutions are dispensed into one ormore of the plurality of vials in a serial fashion.
 34. A method ofselectively purging material from a selective one of a first vial and asecond vial comprising the steps of: a. coupling a waste tube to aselective one of a first drain corresponding to the first vial and asecond drain corresponding to the second vial; and b. forming a pressuredifferential between an interior and an exterior of the selective one ofthe first vial and the second vial, thereby expelling material from theselective one of the first vial and the second vial through the wastetube.